Research Description

Infection with hepatitis. Hepatitis C virus (HCV) is a positive stranded RNA virus and a member of the Flaviviridae family. The virion consists of a nucleo-capsid core (C) and two envelope proteins E1 and E2. At least six non-structural proteins (NS) are involved in transcription, replication and protein processing. The majority of Hep C HCV cases are chronic infections, a minority of which result in cirrhosis of the liver, and possibly hepatic liver cancer.

The only known treatment for hep atitisC is treatment with interferon-alpha (IFN), or more recently combination treatment of IFN-á and the anti-viral drug ribavirin. We have examined the response to interferon-alpha and riabvirin in two groups of patients, Caucasian and Afro-Americans. This was aprt of a large study involving 400 patients at multiple centers. The rate of positive response to treatment is much higher in Caucasian patients(50%) than in African Americans ( 0%) . In general those patients responding to treatment showed higher levels of gene induction after interferon treatment suggesting a defect overall in gene induction in non-responders. This has been termed blunting.The mechanism leading to this sustained response and the lack of response in other patients is not understood. There are several factors involved in response, including age, viral genotype, degree of liver fibrosis , initial levels of HCV and more recently genetic polymorphisms.. In order to study this phenomenon in depth we ran approximately 400 DNA microarrays, measuring the expression of approxiamtely 20,000 genes at multiple time points. This study has been completed and is known as the Virahep C study. A second study with a smaller number of patients using a different interferon gave similar results.

Virus and Human history. Since retiring I have been concentrating on writing a book on the influence of viruses on human history and also a history of virology.